African trypanosomiasis, a devastating disease of humans and livestock, is a major impediment to the development of central Africa. Variant antigen is a parasite product that is presented to the host immune system during an infection with Trypanosoma brucei subspecies. It constitutes most of the surface coat of the parasite, is shed into the plasma in amounts proportional to the level of parasitemia, binds to host blood cells, accumulates in the spleen, and is present as immune complexes. Since all of these conditions are known to affect the quality and quantity of the immune response to conventional antigens, the purpose of this study is to determine what positive and negative effects variant antigen has upon the immune system. Variant antigen from several isolates of T. brucei subspecies will be collected from trypanosomal extracts by ion-exchange chromatography; purity of the preparations assessed by SDS-PAGE and immunoelectrophoresis. The following variables in the administration of variant antigen to inbred mice will be tested: dose, condition, and source of the variant antigen; number and route of its injection and the H-2 haplotype and Ig4- and Ig6-allotype of the experimental hosts. Mice will be assayed at various times after administration for the generation of variant-specific protective or nonprotective immune responses (i.e., delayed hypersensitivity, IgM, TH cell-mediated IgG1,2 or 4. Counterprotection, induced by treatment of mice with variant antigen, will be assayed by measuring polyclonal expansion and production of unelicited antibodies by B cells, polyclonal expansion and stimulation of nonspecific help and/or suppression by T cells, and variant-specific anergy to challenge with antigen or living trypanosomes. If time remains, a secondary characterization will be started to define the cellular circuits and soluble mediators involved in the positive and negative immunological effects of variant antigen. Since the shedding of surface components is a general feature of infectious organisms and tumors, the approach used in this study and the results derived from it may be applicable to acute disease processes in general.